Clofibrate Selectively Induces Azoreduction of Dimethylaminoazobenzene (DAB) by Rat Liver Microsomes

  • W. G. Levine
  • H. Raza
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 197)


Reduction of azo linkages in xenobiotics has long been known in biological systems. Fifty years ago, the antibacterial dye, prontosil, was shown to be reduced to the active product, sulfanilamide, by colonic bacterial. Hernandez et a1.2 found that reduction of prontosil and neotetrazolium by rat liver microsomes is partially inhibited by CO, implying the involvement of cytochrome P-450. Purified NADPH-cytochrome c reductase also catalyzes reduction and accounts for CO-insensitive activity3. Fujita and Peisach4 reported that azoreduction of amaranth is almost completely inhibited by CO and is induced by treatment with phenobarbital (PB) or 3-methylcholanthrene (MC). Under all conditions, the rate of azoreduction of amaranth is proportional to total microsomal cytochrome P-450. Antibodies against PB- and MC-induced cytochrome P-450 almost completely inhibit azoreduction of amaranth in PB- or MC-induced microsomes, respectively6. Recently, it was shown that purified cytochrome P-450 from PB-induced rat livers readily reduces amaranth7. Thus, there are several distinct azoreductases in microsomes which can be distinguished by their substrate spectificities. FMN and FAD markedly stimulate azoreduction of amaranth5 and neoprontosil8. The stimulated activity is unaffected by CO, implying, although not necessarily proving, that cytochrome P-450 is not involved. However, it was later demonstrated that these flavines could transfer electrons from both NADPH-cytochrome c reductase and cytochrome P-450 to dye.9


Lauric Acid Microsomal Cytochrome Reductive Metabolism Hypolipidemic Drug Azoreductase Activity 
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Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • W. G. Levine
    • 1
  • H. Raza
    • 1
  1. 1.Department of Molecular PharmacologyAlbert Einstein College of MedicineBronxUSA

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